TY - JOUR
T1 - A structural characterization of the isoniazid Mycobacterium tuberculosis drug target, Rv2971, in its unliganded form
AU - Shahine, Adam E
AU - Prasetyoputri, Anggia
AU - Rossjohn, Jamie
AU - Beddoe, Travis C
PY - 2014
Y1 - 2014
N2 - Aldo-keto reductases (AKR) are a large superfamily of NADPH-dependent oxidoreductases and play a role in detoxification of toxic metabolites. Rv2971, an AKR in Mycobacterium tuberculosis, has recently been identified as a target of isoniazid, a key first-line drug against tuberculosis. Here, the cloning, expression, purification, crystallization and structural characterization of Rv2971 are described. To gain insight into its function, the crystal structure of Rv2971 was successfully determined to 1.60 A resolution in its unliganded form. The structure exhibits a TIM-barrel fold typical of AKRs, revealing structural characteristics essential for function and substrate specificities, allowing a structural comparison between Rv2971 and other mycobacterial AKRs.
AB - Aldo-keto reductases (AKR) are a large superfamily of NADPH-dependent oxidoreductases and play a role in detoxification of toxic metabolites. Rv2971, an AKR in Mycobacterium tuberculosis, has recently been identified as a target of isoniazid, a key first-line drug against tuberculosis. Here, the cloning, expression, purification, crystallization and structural characterization of Rv2971 are described. To gain insight into its function, the crystal structure of Rv2971 was successfully determined to 1.60 A resolution in its unliganded form. The structure exhibits a TIM-barrel fold typical of AKRs, revealing structural characteristics essential for function and substrate specificities, allowing a structural comparison between Rv2971 and other mycobacterial AKRs.
UR - http://journals.iucr.org/f/issues/2014/05/00/hv5254/hv5254.pdf
U2 - 10.1107/S2053230X14007158
DO - 10.1107/S2053230X14007158
M3 - Article
VL - 70
SP - 572
EP - 577
JO - Acta Crystallographica Section F: Structural Biology Communications
JF - Acta Crystallographica Section F: Structural Biology Communications
SN - 2053-230X
IS - 5
ER -